June 27, 2013
Tiny Molecule Offers Big Hope For Treating Alzheimer’s
Brett Smith for redOrbit.com - Your Universe Online
Researchers at Northwestern University say they have been working with a promising new drug-like molecule that could lead to a preventative treatment for Alzheimer's disease, according to their report in the open access journal PLOS ONE.
"This is the starting point for the development of a new class of drugs," said lead researcher D. Martin Watterson, a professor molecular biology and biochemistry at Northwestern. "It's possible someday this class of drugs could be given early on to people to arrest certain aspects of Alzheimer's."
Dubbed MW108, the unique molecule targets an enzyme that is overactive in patients with Alzheimer's and causes brain inflammation, along with impaired neuron capability. The enzyme, called p38alpha MAPK, has often been overlooked in the search for Alzheimer's treatments, study researchers said.
"We think this protein kinase target is one of the key players in the early to mid-stage development of several diseases of the central nervous system and cancer," Watterson said.
To test the effectiveness of their potential treatment, the scientists first injected mice with beta-amyloid - a telltale symptom of Alzheimer's in humans. One group of these mice was give a dose of MW108 while a control group was given a placebo.
Next, the groups of mice were taught how to navigate through a water maze based on a series of cues. The groups were then placed in an unfamiliar part of the maze to see whether they could find their way through it.
The researchers found that the MW108-treated mice found their way through the maze as quickly as a group that had never received the beta-amyloid injection. The placebo group was actually more prone to mistakes and took longer to find their way through the maze, the study authors reported.
The research team also examined the effects of MW108 on a physiological level - namely, whether it assisted in synaptic signaling.
"That's why we think people with Alzheimer's disease have trouble learning," said study co-author Dr. Ottavio Arancio, a pathologist from Columbia University. "If you can't transmit information from one cell to another, you can't learn."
To test synaptic signaling, Arancio's team removed slices from normally functioning mice brains and incubated them with beta-amyloid or beta-amyloid and MW108. The Columbia team then sent an electrical current through the brain slices and measured the strength of its the synapses.
They found that the synapses that had only been exposed to beta-amyloid transmitted a lower signal that rapidly diminished. The synapses that had also been exposed to MW108, on the other hand, appeared to send a normal signal.
In their conclusion, the study authors noted that MW108 protects the brain in two different ways. The inhibition of p38 MAPK prevents both the disruption of synaptic messaging and the damaging effects on glial cells, where the over activation of p38 MAPK releases damaging neurotoxins and causes inflammation.
"These exciting results provide new hope for developing drugs against an important molecular target in the brain," said Roderick Corriveau, program director at the National Institute of Neurological Disorders and Stroke. "They also provide a promising strategy for identifying small molecule drugs designed to treat Alzheimer's disease and other neurological disorders."